The immune system plays a critical role in the pathogenesis of a wide range of important diseases and conditions, including infection, autoimmunity, allograft rejection and neoplasia. The shortcomings of the immune system in these disorders can be broadly considered as either the failure to develop a sufficiently potent response to a deleterious target or the inappropriate generation of a destructive response against a desirable target. Standard medical treatments for these diseases, including chemotherapy, surgery and radiation therapy, have clear limitations with regard to both efficiency and toxicity. While prevention of the disease or condition would be ideal, these approaches typically have met with little success. New strategies based on specific manipulation of the immune response are greatly needed.